Critical Role Of Proprotein Convertase 6 In Human Uterine Epithelium For Embryo Implantation And Clinical Implications
Funder
National Health and Medical Research Council
Funding Amount
$643,899.00
Summary
Implantation of an embryo into the uterus is a key step for human development. Implantation failure causes embryonic death, pregnancy loss and infertility. Conversely, preventing implantation is an attractive approach for contraception. We have established that proprotein convertase 6 (PC6) is a master regulator of implantation. We will investigate how PC6 works in a woman's uterus, and how we can use this knowledge to improve implantation in IVF and to develop PC6 drugs for new contraceptives.
Novel Roles For Follistatin In Reproductive Biology
Funder
National Health and Medical Research Council
Funding Amount
$630,916.00
Summary
The follistatin protein has important functions throughout the body. Recent studies using mutant mice have identified key roles for follistatin in the development and function of the female reproductive system (ovary, uterus). We will now undertake detailed studies to determine how follistatin regulates these processes. This is relevant to our understanding of the mechanisms causing infection and inflammation in the reproductive tract.
Matrix Metalloproteinases, Leukocytes And Menstruation
Funder
National Health and Medical Research Council
Funding Amount
$191,812.00
Summary
Menstrual bleeding problems are a common cause of pain and discomfort for women and often are satisfactorily treated only by hysterectomy. Despite this, little is known about the processes causing menstruation. Recently, we and others have demonstrated a role for a family of biological catalysts (enzymes) which break down the structure of the tissue lining the uterus (the endometrium) and are thought to cause menstrual bleeding. However, the mechanisms regulating their production during the norm ....Menstrual bleeding problems are a common cause of pain and discomfort for women and often are satisfactorily treated only by hysterectomy. Despite this, little is known about the processes causing menstruation. Recently, we and others have demonstrated a role for a family of biological catalysts (enzymes) which break down the structure of the tissue lining the uterus (the endometrium) and are thought to cause menstrual bleeding. However, the mechanisms regulating their production during the normal menstrual cycle is still largely unknown. Cells which come initially from the blood (leukocytes, particularly neutrophils and eosinophils) dramatically increase in numbers immediately prior to menstruation and these along with other cells, known as mast cells, start to produce a number of factors which we postulate are important for regulation of the enzymes. These cells, are also present in high numbers in endometrium of women with menstrual bleeding problems. This study will demonstrate that both the enzymes, and the leukocytes play a critical role in menstruation and will determine how the leukocytes in the endometrium are regulated. The studies have important implications for understanding and treating menstrual bleeding disorders.Read moreRead less
Brain Angiotensin: Generation, Localisation And Physiological Function
Funder
National Health and Medical Research Council
Funding Amount
$209,250.00
Summary
The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the b ....The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the blood stream because of the blood-brain barrier. Strains of mice in which the genes that code for two components of this system - angiotensin converting enzyme (the enzyme responsible for generating angiotensin II) and angiotensinogen (the protein which gives rise to angiotensin II) provide excellent tools to elucidate this system in the brain. By studying these mice we will be able to determine whether angiotensin converting enzyme is necessary in the brain for foreming angiotensin II, and we will be able to determine the sites in the brain where authentic angiotensin peptides exist. We will also determine whether angiotensin II transmits information between neurons in the brain that play a role in control of the cardiovascular system and body fluid balance.Read moreRead less